MiR-24-3p attenuates IL-1β-induced chondrocyte injury associated with osteoarthritis by targeting BCL2L12
Abstract Background MiR-24-3p has been reported to be involved in an osteoarthritis (OA)-resembling environment. However, the functional role and underlying mechanism of miR-24-3p in chondrocyte injury associated with OA remains unknown. Methods The expression of miR-24-3p was determined using rever...
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| Format: | Article |
| Language: | English |
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BMC
2021-06-01
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| Series: | Journal of Orthopaedic Surgery and Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13018-021-02378-6 |
| _version_ | 1818474194017452032 |
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| author | Jin Xu Xiaozhong Qian Ren Ding |
| author_facet | Jin Xu Xiaozhong Qian Ren Ding |
| author_sort | Jin Xu |
| collection | DOAJ |
| description | Abstract Background MiR-24-3p has been reported to be involved in an osteoarthritis (OA)-resembling environment. However, the functional role and underlying mechanism of miR-24-3p in chondrocyte injury associated with OA remains unknown. Methods The expression of miR-24-3p was determined using reverse transcription quantitative PCR analysis in OA cases and control patients, as well as IL-1β-stimulated chondrocyte cell line CHON-001. The cell viability was analyzed by CCK-8 assay. Apoptosis status was assessed by caspase-3 activity detection. The pro-inflammatory cytokines (TNF-α and IL-18) were determined using ELISA assay. The association between miR-24-3p and B cell leukemia 2-like 12 (BCL2L12) was confirmed by luciferase reporter assay. Results We first observed that miR-24-3p expression level was lower in the OA cases than in the control patients and IL-1β decreased the expression of miR-24-3p in the chondrocyte CHON-001. Functionally, overexpression of miR-24-3p significantly attenuated IL-1β-induced chondrocyte injury, as reflected by increased cell viability, decreased caspase-3 activity, and pro-inflammatory cytokines (TNF-α and IL-18). Western blot analysis showed that overexpression of miR-24-3p weakened IL-1β-induced cartilage degradation, as reflected by reduction of MMP13 (Matrix Metalloproteinase-13) and ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs-5) protein expression, as well as markedly elevation of COL2A1 (collagen type II). Importantly, BCL2L12 was demonstrated to be a target of miR-24-3p. BCL2L12 knockdown imitated, while overexpression significantly abrogated the protective effects of miR-24-3p against IL-1β-induced chondrocyte injury. Conclusions In conclusion, our work provides important insight into targeting miR-24-3p/BCL2L12 axis in OA therapy. |
| first_indexed | 2024-04-14T04:34:44Z |
| format | Article |
| id | doaj.art-2e594363c68047b59a70f5778be8130e |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-04-14T04:34:44Z |
| publishDate | 2021-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-2e594363c68047b59a70f5778be8130e2022-12-22T02:11:55ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2021-06-0116111010.1186/s13018-021-02378-6MiR-24-3p attenuates IL-1β-induced chondrocyte injury associated with osteoarthritis by targeting BCL2L12Jin Xu0Xiaozhong Qian1Ren Ding2Department of Orthopedics, Baoshan District Shanghai Integrated Traditional Chinese and Western Medicine HospitalDepartment of Orthopedics, Shuguang Hospital Baoshan Branch, Shanghai University of Traditional Chinese MedicineDepartment of Orthopedics, Baoshan District Shanghai Integrated Traditional Chinese and Western Medicine HospitalAbstract Background MiR-24-3p has been reported to be involved in an osteoarthritis (OA)-resembling environment. However, the functional role and underlying mechanism of miR-24-3p in chondrocyte injury associated with OA remains unknown. Methods The expression of miR-24-3p was determined using reverse transcription quantitative PCR analysis in OA cases and control patients, as well as IL-1β-stimulated chondrocyte cell line CHON-001. The cell viability was analyzed by CCK-8 assay. Apoptosis status was assessed by caspase-3 activity detection. The pro-inflammatory cytokines (TNF-α and IL-18) were determined using ELISA assay. The association between miR-24-3p and B cell leukemia 2-like 12 (BCL2L12) was confirmed by luciferase reporter assay. Results We first observed that miR-24-3p expression level was lower in the OA cases than in the control patients and IL-1β decreased the expression of miR-24-3p in the chondrocyte CHON-001. Functionally, overexpression of miR-24-3p significantly attenuated IL-1β-induced chondrocyte injury, as reflected by increased cell viability, decreased caspase-3 activity, and pro-inflammatory cytokines (TNF-α and IL-18). Western blot analysis showed that overexpression of miR-24-3p weakened IL-1β-induced cartilage degradation, as reflected by reduction of MMP13 (Matrix Metalloproteinase-13) and ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs-5) protein expression, as well as markedly elevation of COL2A1 (collagen type II). Importantly, BCL2L12 was demonstrated to be a target of miR-24-3p. BCL2L12 knockdown imitated, while overexpression significantly abrogated the protective effects of miR-24-3p against IL-1β-induced chondrocyte injury. Conclusions In conclusion, our work provides important insight into targeting miR-24-3p/BCL2L12 axis in OA therapy.https://doi.org/10.1186/s13018-021-02378-6ChondrocytesInflammationOsteoarthritismiR-24-3p |
| spellingShingle | Jin Xu Xiaozhong Qian Ren Ding MiR-24-3p attenuates IL-1β-induced chondrocyte injury associated with osteoarthritis by targeting BCL2L12 Journal of Orthopaedic Surgery and Research Chondrocytes Inflammation Osteoarthritis miR-24-3p |
| title | MiR-24-3p attenuates IL-1β-induced chondrocyte injury associated with osteoarthritis by targeting BCL2L12 |
| title_full | MiR-24-3p attenuates IL-1β-induced chondrocyte injury associated with osteoarthritis by targeting BCL2L12 |
| title_fullStr | MiR-24-3p attenuates IL-1β-induced chondrocyte injury associated with osteoarthritis by targeting BCL2L12 |
| title_full_unstemmed | MiR-24-3p attenuates IL-1β-induced chondrocyte injury associated with osteoarthritis by targeting BCL2L12 |
| title_short | MiR-24-3p attenuates IL-1β-induced chondrocyte injury associated with osteoarthritis by targeting BCL2L12 |
| title_sort | mir 24 3p attenuates il 1β induced chondrocyte injury associated with osteoarthritis by targeting bcl2l12 |
| topic | Chondrocytes Inflammation Osteoarthritis miR-24-3p |
| url | https://doi.org/10.1186/s13018-021-02378-6 |
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